TY - JOUR A1 - Herkt, Stefanie A1 - Lausen, Olga Nikolaevna A1 - Herglotz, Julia A1 - Schneider, Lucas A1 - Meyer, Annekarin A1 - Pommerenke, Claudia A1 - Salinas-Riester, Gabriela A1 - Seifried, Erhard A1 - Bönig, Halvard-Björn A1 - Lausen, Jörn T1 - Protein arginine methyltransferase 6 controls brythroid Ggene expression and differentiation of human CD34+ progenitor cells T2 - Haematologica N2 - Hematopoietic differentiation is driven by transcription factors, which orchestrate a finely tuned transcriptional network. At bipotential branching points lineage decisions are made, where key transcription factors initiate cell type-specific gene expression programs. These programs are stabilized by the epigenetic activity of recruited chromatin-modifying cofactors. An example is the association of the transcription factor RUNX1 with protein arginine methyltransferase 6 (PRMT6) at the megakaryocytic/erythroid bifurcation. However, little is known about the specific influence of PRMT6 on this important branching point. Here, we show that PRMT6 inhibits erythroid gene expression during megakaryopoiesis of primary human CD34+ progenitor cells. PRMT6 is recruited to erythroid genes, such as glycophorin A. Consequently, a repressive histone modification pattern with high H3R2me2a and low H3K4me3 is established. Importantly, inhibition of PRMT6 by shRNA or small molecule inhibitors leads to upregulation of erythroid genes and promotes erythropoiesis. Our data reveal that PRMT6 plays a role in the control of erythroid/megakaryocytic differentiation and open up the possibility that manipulation of PRMT6 activity could facilitate enhanced erythropoiesis for therapeutic use. Y1 - 2017 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/46391 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-463918 SN - 1592-8721 SN - 0390-6078 N1 - ©2018 Ferrata Storti Foundation. Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher. VL - 103 IS - 1 SP - 18 EP - 29 PB - Ferrata Storti Found CY - Pavia ER -